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Clinicopathological associations of hemispheric dominance in primary progressive apraxia of speech

Eur J Neurol. 2023 Mar 3. doi: 10.1111/ene.15764. Online ahead of print.


OBJECTIVE: Primary progressive apraxia of speech (PPAOS) is associated with imaging abnormalities in lateral premotor cortex (LPC) and supplementary motor area (SMA). It’s unknown whether relatively greater involvement of these regions in either hemisphere is associated with demographics, presenting, and/or longitudinal features.

METHODS: In 51 prospectively recruited PPAOS patients who completed [18 F]-fluorodeoxyglucose (FDG) PET we classified patients as left-dominant, right-dominant, or symmetric, based on visual assessment of the LPC and SMA on FDG-PET. SPM and statistical analysis of regional metabolic values were performed. Diagnosis of PPAOS was made if AOS was present and aphasia absent. Thirteen patients completed Ioflupane-123I (DAT) scans. We compared cross-sectional and longitudinal clinicopathological, genetic, and neuroimaging characteristics across the three groups, with area under the receiver operator curve (AUROC) determined as a measure of effect size.

RESULTS: 49% of the PPAOS patients were classified as left-dominant, 31% as right-dominant, and 20% as symmetric which was supported by results from the SPM and regional analyses. There were no differences in baseline characteristics. Longitudinally, right-dominant PPAOS showed faster rates of progression of ideomotor apraxia (AUROC=0.79), behavioral disturbances (AUROC=0.84), including disinhibition symptoms (AUROC=0.82) and negative behaviors (AUROC=0.82), and Parkinsonism (AUROC=0.75), compared to left-dominant PPAOS. Symmetric PPAOS showed faster rates of dysarthria progression compared to left-dominant (AUROC=0.89) and right-dominant PPAOS (AUROC=0.79). Five patients showed abnormal DAT uptake. Braak neurofibrillary tangle stage differed across groups (p=0.01).

CONCLUSIONS: Patients with PPAOS and a right-dominant pattern of hypometabolism on FDG-PET have fastest rates of decline of behavioral and motor features.

PMID:36869612 | DOI:10.1111/ene.15764

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